Hybrid cholecystokinin-A antagonists based on molecular modeling of

J . Med. Chem. 1992,35, 1042-1049

1042

angiotensinogen), 50 pL of maleate buffer (pH 6.0), 5 pL of phenylmethanesulfonyl fluoride (PMSF), and 2 pL of an appropriate concentration of inhibitor in a dimethylsulfoxide (DMSO) vehicle. Incubation was for 60 min at 37 OC. Following incubation, each mixture was analyzed (in duplicate) for angiotensin I via radioimmunoassay using 1261-labeledangiotensin I and carried out in tubes coated with rabbit antiangiotensin I antibody (Gamma Coat RIA Kit, Dade Clinical h a y s ) . Monkey plasma renin activity ranged from 3-8 ng AI per mL per h. Values for inhibitor t u b were compared to vehicle (DMSO) control tubes to estimate percent inhibition. At the concentrationused, DMSO inhibits the generation of angiotensin I by